Thursday, December 23, 2010

On December 17 Fred Hutchinson Cancer Research Center and its licensees (Argus Genetics and Mars, Inc.) sued MMI Genomics for infringement of a patent directed towards methods of using genetic testing to identify the breed of the dog (US patent 7,729,863). According to the complaint, MMI Genomics is a company based in Davis, California that provides dog breed identification services associated with its Canine Heritage XL Breed Test product.

Some of the claims in the asserted patent raise interesting issues of patent eligibility, particularly in view of the recent Bilski and Prometheus decisions, both discussed extensively on this blog, and the pending appeal of AMP v. PTO (the ACLU challenge to Myriad’s BRCA gene patents). For example, consider claim 1.

1. A method for determining the contributions of canid populations to a canid genome, comprising: (a) genotyping a sample obtained from a test canid to determine the identity of one or both alleles present in the test canid genome for each of a set of markers, wherein the set of markers is indicative of the contributions of canid populations to the genome of the test canid; (b) using a specifically programmed computer comprising an algorithm to compare the identity of one or both alleles for each of the set of markers determined to be present in the test canid genome to a database comprising a plurality of canid population profiles, wherein each canid population profile comprises genotype information for the set of markers in the canid population; and (c) determining the contributions of canid populations to the test canid genome.

The heart of the claimed method seems to reside in applying an algorithm to genotype information using information derived there from to determine the contribution various dog breeds to dog being tested. If that were all the claim covered, I think under Bilski and Prometheus a court would likely find the claim patent ineligible for embodying a fundamental principle. The fundamental principle might be characterized as an abstract idea, or as a natural phenomenon, either would work.

But the claim includes two elements that might be sufficient to render the claim patent eligible: (1) the step of genotyping a sample taken from the dog, and (2) the use of a "specifically programmed computer." In Prometheus, the Federal Circuit relied heavily on the machine or transformation test in arriving at the conclusion that the claims at issue in that case were patent eligible. I believe that even though the Supreme Court clarified in Bilski that the machine or transformation test is not the only test for patent eligibility, it did acknowledge that the test can be a useful and informative tool for assessing patent eligibility, and I predict that the Federal Circuit will continue to rely heavily on the machine or transformation test when faced with claims such as this, as it did in Prometheus.

Under Prometheus and Bilski, I think this one could come out either way. On the one hand, a court could find that genotyping is inherently transformative, because it necessarily involves physical manipulation of biological samples, in the same way that the step of "determining drug metabolite level” was found transformative in Prometheus, and sufficient to render the claim patent eligible. A court could also find that the use of a "specifically programmed computer" satisfies the machine prong of the machine or transformation test.

On the other hand, a court could characterize the genotyping step as mere data-gathering, i.e., "insubstantial extra-solution activity,” and thus ignore it in the analysis. This is what the Federal Circuit did in In re Grams, and as noted in my previous blog post the Federal Circuit explicitly held in Prometheus that Grams is still good law. In Prometheus, the Federal Circuit distinguish the two cases by pointing out that in Grams the focus of the invention is on the algorithm itself, and that the data-gathering step generically covered many different types of clinical diagnostic tests, whereas the Prometheus claims were targeted to specific drugs and specific diseases. The dog breed testing claim seems to fall somewhere in between. I think a court could go either way, by either stressing that the claim focuses on the algorithm and is not limited to any specific genotype or genetic test, in which case the claim is patent ineligible under Grams, or by stressing that the genotyping step is "central to the purpose" of the claim and thus sufficient to render the claim patent eligible under Prometheus.

Regarding the use of a computer, it is important to note that under In re Bilski the machine or transformation test requires the involvement of a "particular" machine, and many have speculated that a general-purpose computer would not satisfy this requirement of "particularity." Whoever drafted the dog breed testing claim wisely specified that the computer used in the method is "specifically programmed," but I'm not sure if that will be sufficient. A court could dismiss the "specifically programmed" language and find that the mere involvement of the computer does not satisfy the "particularity” aspect of the machine or transformation test.

Claim 35 is similar to claim 1, but instead of reciting the use of a computer, includes a step of "applying a computer-implemented statistical model.” This claim could be more vulnerable than claim 1, since it does not appear to explicitly recite the use of a particular machine.

There are also a number of dependent claims limited to specific SNP markers, specific dog breeds, etc., and these claims should face less of a threat of invalidation for lack of patent eligibility. Patent eligibility analysis often hinges on an assessment of whether the claim preempts all substantial practical uses of an abstract idea or natural phenomenon, so logically the narrower a claim is the more likely it is not preemptive, and thus patent eligible. Although in Bilski the Supreme Court apparently rejected this logic, because it held even relatively narrow dependent claims to be patent ineligible even though they clearly did not preempt all uses of risk hedging (the fundamental principle at issue in that case).

Claim 36 appears to be a Beauregard claim, a claim directed toward computer readable medium on which a computer program is inscribed. It would be interesting to see how this claim holds up, it is my understanding that the status of this sort of claim has not been entirely resolved post-Bilski, I saw some posts on this topic on Patently-O a while back.

36. A computer readable medium comprising stored thereon: (a) a data structure stored thereon for use in distinguishing canid populations, the data structure comprising: (i) a marker field, which is capable of storing the name of a marker or of an allele of the marker; and (ii) a genotype information field, which is capable of storing genotype information for the marker in a canid population, wherein a record comprises an instantiation of the marker field and an instantiation of the genotype information field and a set of records represents a canid population profile; and (b) computer-executable instructions for implementing a method for determining the contributions of canid populations to a canid genome, comprising: (i) obtaining the identity of one or both alleles in a test canid genome for each of a set of markers; and (ii) determining the contributions of canid populations to the test canid genome by comparing the alleles in the test canid genome to a database comprising canid population profiles, wherein each canid population profile comprises genotype information for the set of markers in the canid population.

Claim 37 seems even more problematic to me. I don't know that it can be called a Beauregard claim, it appears to basically be directed toward a computer readable medium on which a data structure is stored, which I am guessing is not the same thing as a computer program. I would be particularly interested in seeing how court deals with this claim.

37. A computer-readable medium comprising a data structure stored thereon for use in distinguishing canid populations, the data structure comprising: (a) a marker field, which is capable of storing the name of a marker or of an allele of the marker; and (b) a genotype information field, which is capable of storing genotype information for the marker in a canid population, wherein a record comprises an instantiation of the marker field and an instantiation of the genotype information field and a set of records represents a canid population profile, wherein the marker field comprises a set of markers indicative of the contributions of canid populations to the genome of a test canid.

Friday, December 17, 2010

Today a panel of the Federal Circuit issued a decision in Prometheus v. Mayo, an important case involving the application of the patent eligibility doctrine to biotechnology, and more particularly molecular diagnostic testing and personalized medicine. I have discussed this case in numerous previous blog posts, see for example here.

BackgroundIn a nutshell, the case involves claims directed towards methods for optimizing the amount of drug administered to a specific patient, an example of personalized medicine. The claims are limited to certain categories of thiopurine drugs used to treat immune-mediated gastrointestinal disorders such as Crohn's disease, the use of which is often accompanied by serious adverse side effects, including hepatotoxicity. Because different patients metabolize the drug differently, it had been difficult for doctors to ascertain the proper dosage, and some doctors had reportedly been hesitant to prescribe the drugs at all for fear of toxic side effects.

The challenged claims are directed towards methods that all comprise a step of determining the level of thiopurine drug metabolite in a patient sometime after administering the drug to the patient, and based on the result of that determination recognizing that the dosage of drug administered to the patient should be increased or reduced, i.e.,a determination that the level of drug metabolite exceeds a certain threshold would indicate that the dosage should be decreased, and vice versa. Many of the claims also explicitly recite a step of administering the drug to the patient.

A district court judge, in an opinion clearly influenced by Judge Breyer's provocative dissent in LabCorp, held the claims patent ineligible for allegedly wholly preempting a "natural phenomenon." In its analysis, the judge dismissed the steps of administering drug and determining drug metabolite level as mere "data-gathering steps," irrelevant to the patent eligibility of the claim.

The case was appealed to the Federal Circuit, but before the appeal was decided the Federal Circuit issued its en banc In re Bilski decision (Bilski I) which held the machine or transformation test to be the definitive test for patent eligibility of method claims.

On appeal the Federal Circuit panel reversed and held that the Prometheus claims satisfied applied the newly minted Bilski machine or transformation test. In particular, the panel held that the steps of administering drug to the patient and determining drug metabolite level were both inherently and independently sufficient to satisfy the transformation prong of the machine or transformation test. In contrast with the district court, which dismissed these steps as mere data-gathering, the Federal Circuit characterized the administering and determining steps as central to the purpose of the claim and thus relevant to the question of patent eligibility.

But shortly thereafter, in Bilski v. Kappos (Bilski II), the Supreme Court overturned Bilski I to the extent that it had characterized the machine or transformation test as the definitive test for patent eligibility, and reiterated that the sole and fundamental test for patent eligibility is whether the claim "patents" a fundamental principle, i.e., laws of nature, physical phenomena and abstract ideas. The Supreme Court then vacated the Federal Circuit's decision in Prometheus v. Mayo and remanded the case to the Federal Circuit to decide in a manner consistent with Bilski II.

Today's Post-Bilski II Prometheus Decision
Today's Federal Circuit decision on remand comes to the same conclusion as the first, reversing the district court and holding all of the challenged claims to be patent eligible. The court's analysis is also virtually identical to the original decision, focusing primarily on the transformative nature of the administering and determining steps.

It is important to bear in mind that while Bilski II rejected the notion that the machine or transformation test is the only test for patent eligibility of method claims, it did acknowledge that the machine or transformation test is in many instances highly probative of the fundamental inquiry. Significantly, the Supreme Court did not offer up any other alternative test for determining whether a claim "patents a fundamental principle." As noted by the en banc Federal Circuit in Bilski I, as a practical matter it can be extremely difficult to apply this fundamental test to actual claims, which is why the Federal Circuit tried to institute the use of a definitive machine or transformation test as a more objective and easier to administer proxy for the ultimate inquiry. As a practical matter of expedience, I have predicted that the courts and PTO will continue to rely heavily on the machine or transformation test post-Bilski II.

In today's decision, the Federal Circuit panel pointed out that under Bilski II the scope of patent eligible subject matter remains quite broad, and that while fundamental principles are not patent eligible "particular applications" of fundamental principles are. Applying this standard, the panel held that Prometheus' claims do not preempt the correlations between drug metabolite level and optimal dosage, but rather utilize them in "the treatment of a specific disease by administering specific drugs and measuring specific metabolites."

The panel also emphasized the continuing relevance of the machine or transformation test, pointing out that the Supreme Court had characterize it as a "useful and important clue, an investigative tool" for determining patent eligibility. It then came to the same conclusion as it did in its pre-Bilski II decision, finding that both the administering and determining steps were each inherently and independently sufficient to confer patent eligibility on the claims. In view of this determination, the panel found it unnecessary to address the question of whether the claims satisfy the machine prong of the test.

The panel emphasized that if the claims had not included a step of administering a drug or determining the level of drug metabolite, but had merely recited recognizing the correlation between drug metabolite level and the desirability of modifying the dosage (i.e., the "wherein" clauses of the claims), then the claims would have been patent ineligible for claiming nothing more than "mental steps." But by including a step of administering a drug and/or determining the level of drug metabolite, transformative steps which are "central to the purpose" of the method, the claim is rendered patent eligible.

In effect, Bilski II had essentially on effect on the outcome of the Prometheus appeal. Fortunately, the Supreme Court decided Bilski II in a manner allows a great deal of discretion for the Federal Circuit and lower courts. This panel of the Federal Circuit clearly sees the importance of permitting the patenting of diagnostic methods and methods of treating patients with drugs, and sought to maintain their patent eligiblity by emphatically establishing that method claims reciting a step of administering a specific class of drugs to a patient, or of performing a molecular diagnostic test of the patient, are patent eligible per se.

However, the panel is also emphatic that claims that could be potentially infringed by merely thinking about or recognizing a physiological correlation cannot be patented, a hypothetical scenario that some critics of gene patents and patents on diagnostic tests often point to.

The one aspect of the decision that I found less than entirely convincing was the panel's attempt to distinguish over the holding in In re Grams, a 1989 Federal Circuit decision. Grams was a case involving the patent eligibility of claims reciting methods that basically involved (1) performing a clinical diagnostic test on an individual patient, and (2) applying an algorithm to the data generated by the test in order to determine whether an abnormality exists, and possible causes of the abnormality. In Grams, the data-gathering steps were disregarded in the court's patent eligibility analysis, and the claims held patent ineligible for "in essence" claiming nothing more than a patent ineligible algorithm.

In a sense, the Grams claims are highly analogous to the Prometheus claims. The determining step in the Prometheus claims involves nothing more than performing a clinical diagnostic tests on individual patient, and the step of using the results to determine whether drug dosage should be altered is nothing more than a simple algorithm. According to the Prometheus panel, the distinction lies in the fact that in Grams the "essence" of the claimed process is the algorithm, and that the Gram patent "focused only on the algorithm rather than a clinical test." I'm not sure how convincing this distinction is, perhaps the panel could have been more straightforward and acknowledged the tension between Grams and Prometheus.

However, I have read the Grams decision and think a plausible distinction is that the Prometheus claims are limited to diagnostic tests for a limited number of specified of drug metabolites, while in Gram the claim appears to broadly encompass any of a host of clinical tests to which the algorithm could be applied. This suggests that if the Prometheus claims had been drafted more broadly to encompass any drug and drug metabolite, rather than being restricted to specific classes of thiopurine drugs, the claims could have been found patent ineligible. In effect, the distinction between the Grams and Prometheus claims is a matter of claim scope, something I think would be better addressed using the enablement requirement rather than patent eligibility, as I argued in the amicus brief I filed with Robert Cook-Deegan in the Myriad gene patent case.

Finally, what are the implications of today's Prometheus decision for the patent eligibility of the genetic diagnostic method claims at issue in the Myriad gene patent case (Association for Pathology v. US Patent and Trademark Office)? Today's decision does not alter my previous prediction, which is that the outcome will depend upon how the Federal Circuit interprets the scope of Myriad's patent claims. If the Federal Circuit adopts the ACLU's broad interpretation the claims (which is the interpretation the district court judge accepted for his analysis), pursuant to which the claims broadly cover the purely mental process of analyzing genetic information, then under Prometheus I believe the claims must be found patent ineligible. Alternatively, if the Federal Circuit adopts Myriad’s interpretation of its claims, under which the claims are limited to methods that involve physically isolating and analyzing DNA molecules, I think under Prometheus the claims should be found patent eligible by virtue of comprising a transformative step (highly analogous to the administering step in the Prometheus claims) central to the purpose of the claimed methods.

Tuesday, December 7, 2010

An amici brief was filed yesterday by Professors Lori Andrews and Joshua Sarnoff on behalf of the American Medical Association, American Society of Human Genetics, American College of Obstetricians and Gynecologists, American College of Embryology, and the Medical Society of the State of New York, arguing for affirmance of the district court's decision in AMP v. PTO. Professor Andrews has for years been one of the most outspoken critics of gene patents, and was involved with a bill introduced in Congress in 2007 that if enacted would have broadly prohibited the patenting of DNA-based inventions.

Their brief is more alarmist than the brief submitted by the ACLU/PubPat, arguing that gene patents have cost patient's their lives, and the healthcare system billions of dollars. For example, allege that gene patents are being asserted against physicians across the country, and that physicians have to worry about infringing patents based on nothing more than mere "conscious thoughts." They also contend that gene patents are killing patients. For example, they state that drug companies have used these patents to prevent use of genetic testing to determine whether a drug will help or harm patients, to block the availability of genetic testing (which they allege resulted in the of a 10-year-old patient), and to force patients to use poor quality diagnostic tests rather than improved alternatives (which they allege resulted in a patient undergoing unnecessary removal of ovaries based on erroneous BRC genetic test result).

The AMA et al. adopt a very broad definition of the diagnostic method claims, under which they would be infringed by anyone merely "reading and thinking about the sequence data disclosed in the patent." As discussed in a previous post, this is a much broader interpretation of the claims than Myriad has proffered.

They also argue that patents are not necessary to incentivize the discovery of genetic mutations correlated with disease or the commercialization of diagnostic testing based on these discoveries, citing to the Sec.'s Advisory Committee on Genetics, Health and Society (SACGHS) Report.

In the amici brief submitted by me and Robert Cook-Deegan, we argued that regardless of whether patents are necessary to incentivize the development of genetic diagnostic testing for Mendelian traits, in which mutations in a single gene are highly correlated with a specific disease, they quite likely will be necessary for the optimal development of next-generation genetic diagnostic testing involving much more complex relationships and multiple genes, or if FDA imposes heightened regulation on diagnostic testing. We also argued that a decision broadly rendering gene patents patent ineligible could have serious unintended negative consequences for biotechnology, particularly outside the realm of Mendelian genetic diagnostic testing, and that there are other more focused approaches for dealing with problematic gene patents or gene patent enforcement activities. The AMA brief does not address these points, but rather seems to assume that the only available mechanisms for dealing with problems associated with gene patents is a broad prohibition extending far beyond Myriad and BRCA testing.

Monday, December 6, 2010

After reading the briefs submitted by Myriad and the ACLU/PubPat in AMP v. PTO (the challenge to Myriad’s gene patents, described in previous posts to this blog), one thing that struck me was that the parties do not appear to disagree over the patent eligibility of genetic diagnostic methods. In fact, with respect to these method claims, the only dispute is with respect to the proper interpretation of the claims.

The challenged diagnostic method claims recite processes of either "analyzing" or "comparing" nucleotide sequences. For example, claim 1 of US patent number 6,033,857 claims:

A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequence identifies a mutant BRCA2 nucleotide sequence.

Myriad argues for a relatively narrow interpretation of the claims, under which the claims are limited to methods which require actual physical analysis of DNA molecules. Under their interpretation, the term "nucleotide sequence," as used in the claims, refers to actual polynucleotides, i.e., DNA or RNA molecules, and the step of comparing these molecules necessarily requires physically isolating polynucleotides from a patient's tissue sample, and then processing and analyzing the molecules. Myriad argues that these processes are all clearly transformative of physical molecules, and because the transformations are “central to the purpose of the claims,” the claims satisfy the machine or transformation test. They cite to Prometheus for the proposition that transformative steps that are central to the purpose of the claims cannot be disregarded in the analysis as mere "data-gathering steps,” and argue these transformative steps render the claim patent eligible.

The ACLU, on the other hand, argues for a much broader interpretation of the method claims. They argue that the term "nucleotide sequence" in the claims refers to sequence information, not to molecules, and that the claims cover the purely mental process of "comparing" or "analyzing" DNA sequence information. Under this broad interpretation, the claims clearly do not require any sort of physical transformation, and on this basis the ACLU argues they fail the machine or transformation test, which they correctly note remains "a useful and important clue" to patent eligibility (using the language of the Supreme Court).

Interestingly, the ACLU never suggests in their brief that the diagnostic method claims would be patent ineligible if limited to methods involving actual isolation and processing of DNA molecules, i.e., the only processes covered by the claims under Myriad's interpretation of the claims. Conversely, Myriad never argues that a method claim that encompasses purely mental processes for comparing DNA sequence information would be patent eligible. Thus, both parties seem implicitly to agree on a consensus approach under which a claim directed toward a genetic diagnostic method is patent eligible if limited to diagnostic methods that involve actual isolation and manipulation of DNA molecules, but patent ineligible if the claim would also cover merely comparing DNA sequence information.

Notably, the district court adopted the ACLU's broad interpretation of the claims, and held that the claims cover a process of comparing or analyzing DNA sequence information. However, in dicta the district court went even further, stating that "[e]ven if the challenged claims were read to include the transformations associated with isolating and sequencing human DNA, these transformations would constitute no more than ‘data-gathering step[s]’ that are not central to the purpose of the claimed process.. . . . Consequently, even if the method claims-in-suit were construed to include the physical transformations associated with isolating and sequencing DNA, they would still fail the ‘machine or transformation’ test under Section 101 for subject matter patentability."

In my analysis of the district court decision, I pointed out that this dicta seems clearly wrong, and is inconsistent with the Federal Circuit's decision in Prometheus. Clearly, these data-gathering steps are central to the purpose of the claim and should be included in the machine or transformation analysis. I suspect that the ACLU agrees with my assessment, and is not even trying to argue for more extreme position taken by the district court.

It seems to me that the implicit consensus between Myriad and the ACLU is correct, i.e., method of genetic diagnostic claims are patent eligible if they include steps involving the actual physical manipulation of DNA molecules, but patent ineligible if they would cover the wholly mental process of analyzing DNA sequence information.

As a side note, another point of contention regarding claim interpretation exists with respect to whether some of the claims are limited to cDNA molecules. In its amicus brief, the United States government has argued that claims to isolated genomic DNA are patent ineligible, but claims limited to cDNA molecules are patent eligible (as reported in an earlier post to this blog). For some reason, in its brief the ACLU argues that the United States is mistaken, and that none of the challenged claims is limited to cDNA. ACLU seems to be clearly mistaken on this point--for example, Claim 2 of US patent 5,747,282 (one of the challenged claims) recites "DNA [having] the nucleotide sequence set forth in SEQ ID NO:1.” The Sequence Listing section of the patent specification explicitly identifies SEQ ID NO:1 as a cDNA.

About Me

I am a law professor at the University of Missouri-Kansas City School of Law. My primary research interests lie at the intersection of biotechnology and intellectual property. This blog provides analysis and commentary on recent developments relevant to this area of the law.